In vitro testiranje združenog djelovanja kemoterapeutika i sintetskih liganada za receptor TLR7 u staničnoj liniji H1299

master's thesis

• Title (english): In vitro testing of the chemoterapeutic activity in the presence of TLR7 receptor ligands in H1299 lineage
• Author: Ana Vukić
• Mentor: Jelena Knežević (mentor)
• Mentor: Nada Oršolić (sumentor)
• Committee member: Nada Oršolić (predsjednik povjerenstva)
• Committee member: Inga Marijanović (član povjerenstva)
• Committee member: Martina Šeruga Musić (član povjerenstva)
• Committee member: Sofia Ana Blažević (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2020-02-24, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Karcinom pluća drugi je najčešće dijagnosticirani maligni tumor i najčešći uzrok smrti kod muškaraca i ţena u svijetu kada su u pitanju zloćudne bolesti. Pušenje predstavlja najveći rizik za njegov razvoj, ali nastanak tumora se moţe potaknuti i respiratornim bolestima te virusnim i bakterijskim infekcijama koje dovode do upalnih procesa koji mogu pogodovati razvoju tumora. UroĎeni imunosni sustav vaţan je za prvi odgovor organizma na infekciju patogenima, a u njegovoj aktivaciji ključnu ulogu imaju Toll-like receptori (TLR) koji prepoznaju patogenu pridruţene molekularne sljedove i potiču signalizaciju koja će dovesti do imunosnog odgovora. Endosomski receptor TLR7 aktiviraju jednolančane virusne RNA, ali i sintetski ligandi. Eksprimiran je u stanicama imunosnog sustava, ali i epitelnim te tumorskim stanicama. Cilj ovog diplomskog rada bio je istraţiti kako u in vitro uvjetima stanice metastatskog tumora pluća (H1299) odgovaraju na terapiju citostaticima (cisplatina, karboplatina i paklitaksel) i sintetskim ligandima za receptor TLR7 (resiquimod i imiquimod). Dokazana je ekspresija receptora TLR7 na razini mRNA i proteina u staničnoj liniji H1299 lančanom reakcijom polimerazom u stvarnom vremenu i westernskom metodom detekcije proteina. Pokazali smo da imiquimod u kombinaciji s cisplatinom i paklitakselom značajno smanjuje vijabilnost stanica, dok je utjecaj resiquimoda na citotoksičnost vrlo slab.

Abstract (english)

Lung cancer is the leading cause of cancer deaths and second most common diagnosed malignant tumor in both men and women. Smoking is the number one risk factor for lung cancer, but enviromental and genetic factors and respiratory diseases increase the chance of developing it as well. Bacterial and viral infections can lead to frequent inflammations linked to tumor progression. Innate immune system can be activated immediately after pathogen invasion. Activation of Toll-like receptors (TLRs) that recognize pathogen-associated molecular patterns (PAMPs) causes the initial immune response. TLR7 is an endosomal receptor activated by viral ssRNAs and synthetic ligands. It is expressed in different types of immune cells, as well as epithelial and tumor cells. The aim of this research was to determine the effects of TLR7 ligand (resiquimod and imiquimod) and cytostatic (cisplatin, carboplatin, paclitaxel) combined therapy on H1299 human metastatic cell lineage. We have shown the presence of TLR7 mRNA and proteins expression in H1299 cells using RT-qPCR and Western blot. We have shown that imiquimod in combination with cisplatin and paclitaxel significantly reduces H1299 cell viability, while combined treatment with resiquimod had low cytotoxic effect.

• Keywords: tumor pluća; TLR7; resiquimod; imiquimod; kemoterapeutici; citotoksičnost
• Keywords (english): lung cancer; TLR7; resiquimod; imiquimod; chemotherapeutics; citotoxicity
• Language: croatian
• URN:NBN: urn:nbn:hr:217:798897
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2021-02-24
• Created on: 2020-06-09 10:17:54